Abstract
Epidemiological studies show that sulfur dioxide (SO2), a major air pollutant, is associated with the morbidity and mortality of respiratory tract diseases. The aim of the present study was to determine the effects of SO2 on mitochondria and the corresponding molecular characterization in the lung. Male Wistar rats were exposed to 0, 3.5, 7, and 14 mg/m3 SO2 (4 h/day, 30 days). Mitochondrial dysfunction including decreases of cytochrome c oxidase (COX) activity and mitochondrial membrane potential (MMP) was observed in the lungs of rats after SO2 inhalation. We showed that total mitochondrial DNA (mtDNA) content was significantly decreased in the lungs from rats exposed to SO2. Furthermore, SO2 repressed the expression of complex IV and V subunits encoded by both nuclear DNA (nDNA) and mtDNA. Moreover, such changes were accompanied by depressions of three regulatory factors: peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The findings suggest that SO2 exposure induced mitochondrial dysfunction in rat lungs. Both nDNA and mtDNA are involved in SO2-induced depression of mitochondrial biogenesis in the lungs. There might be a tissue-specific response of mitochondrial biosynthesis to SO2 inhalation. Such impairment may lead to cellular dysfunction and eventually lung diseases.







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References
Amo T, Sato S, Saiki S, Wolf AM, Toyomizu M, Gautier CA, Shen J, Ohta S, Hattori N (2011) Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects. Neurobiol Dis 41:111–118
Aravamudan B, Thompson MA, Pabelick CM, Prakash YS (2013) Mitochondria in lung diseases. Expert Rev Respir Med 7(6):631–646
Bai J, Meng Z (2010) Expression of caspase and apoptotic signal pathway induced by sulfur dioxide. Environ Mol Mutagen 51:112–122
Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landázuri MO, Enríquez JA (2012) NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab 16:378–386
Beck-Speier I, Hinze H, Holzer H (1985) Effect of sulfite on the energy metabolism of mammalian tissues in correlation to sulfite oxidase activity. Biochim Biophys Acta 841(1):81–89
Bhaskaran K, Hajat S, Haines A, Herrett E, Wilkinson P, Smeeth L (2009) The effects of air pollution on the incidence of myocardial infarction—a systematic review. Heart 95:1746–1759
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Chen H, Goldberg MS, Villeneuve PJ (2008) A systematic review of the relation between long-term exposure to ambient air pollution and chronic diseases. Rev Environ Health 23:243–297
Dutch Expert Committee on Occupational Standards, (2003), Sulphur dioxide; health-based recommended occupational exposure limit, 5th ed. (ISBN 90-5549-507-7). Health Council of the Netherlands Press, Hague.
El-Dars FM, Mohamed AM, Aly HA (2004) Monitoring ambient sulfur dioxide levels at some residential environments in the greater Cairo urban region—Egypt. Environ Monit Assess 95:269–286
Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, Jen J, Sidransky D (2000) Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287:2017–2019
Frezza C, Gottlieb E (2009) Mitochondria in cancer: not just innocent bystanders. Semin Cancer Bio 19:4–11
Hayatsu H, Miller RC Jr (1972) The cleavage of DNA by the oxygen-dependent reaction of bisulfite. Biochem. Biophys Res Commun 46:120–124
Hayatsu H, Miura A (1970) The mutagenic action of sodium bisulfite. Biochem Biophys Res Commun 39:156–160
Javadov S, Purdham DM, Zeidan A, Karmazyn M (2006) NHE-1 inhibition improves cardiac mitochondrial fuction through regulation of mitochondrial biogenesis during postinfarction remodeling. Am J Physiol Heart Circ Physiol 291:1722–1730
Longo BM, Rossignol A, Green JB (2008) Cardiorespiratory health effects associated with sulphurous volcanic air pollution. Public Health 122:809–820
McMurchie EJ, Gibson RA, Charnock JS, McIntosh GH (1984) A comparison of mitochondrial respiration and membrane lipid composition in the rat and marmoset following dietary lipid supplementation. Comp Biochem Physiol B 78:817–826
Meng Z, Liu Y (2007) Cell morphological ultrastructural changes in various organs from mice exposed by inhalation to sulfur dioxide. Inhal Toxicol 19:543–551
Meng Z, Zhang B (1999) Polymerase chain reaction-based deletion screening of bisulfite (sulfur dioxide)-enhanced gpt-mutants in CHO-AS52 cells. Mutat Res 425:81–85
Meng Z, Qin G, Zhang B, Geng H, Bai Q, Bai W, Liu C (2003) Oxidative damage of sulfur dioxide inhalation on lungs and hearts of mice. Environ Res 93:285–292
Meng Z, Qin G, Zhang B, Bai J (2004) DNA damaging effects of sulfur dioxide derivatives in cells from various organs of mice. Mutagenesis 19:465–468
Meng Z, Li R, Zhang Z (2005a) Levels of sulfite in three organs from mice exposed to sulfer dioxide. Inhal Toxicol 17:309–313
Meng Z, Liu Y, Wu D (2005b) Effect of sulfur dioxide inhalation on cytokine levels in lungs and serum of mice. Inhal Toxicol 17:303–307
Meng Z, Qin G, Zhang B (2005c) DNA damage in mice treated with sulfur dioxide by inhalation. Environ Mol Mutagen 46:150–155
Meng Z, Qin G, Bai J, Zhang J, Yang Z, Zhang X (2007) Alterations of gene expression profiles induced by sulfur dioxide in rat lungs. Front Biol China 2:369–378
Migliore L, Coppedè F (2009) Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res 674:73–84
Mottley C, Mason RP, Chignell CF, Sivarajah K, Eling TE (1982) The formation of sulfur trioxide radical anion during the prostaglandin hydroperoxidase-catalyzed oxidation of bisulfite (hydrated sulfur dioxide). J Biol Chem 257:5050–5055
Pagano DA, Zeiger E, Stark AA (1990) Autoxidation and mutagenicity of sodium bisulfite. Mutat Res 228:89–96
Picca A, Pesce V, Fracasso F, Joseph AM, Leeuwenburgh C, Lezza AM (2014) A comparison among the tissue-specific effects of aging and calorie restriction on TFAM amount and TFAM-binding activity to mtDNA in rat. Biochim Biophys Acta 1840:2184–2191
Qin G, Wang J, Huo Y, Yan H, Jiang C, Zhou J, Wang X, Sang N (2012) Sulfur dioxide inhalation stimulated mitochondrial biogenesis in rat brains. Toxicology 300:67–74
Reist M, Jenner P, Halliwell B (1998) Sulphite enhances peroxynitrite-dependent alpha1-antiproteinase inactivation. A mechanism of lung injury by Sulphur dioxide. FEBS Lett 423:231–234
Sandstrom T, Stjernberg N, Andersson MC, Kolmodin-Hedman B, Lindstrom K, Rosenhall L (1989) Cell response in bronchoalveolar lavage fluid after sulfur dioxide exposure. Scand J Work Environ Health 15:142–146
Sang N, Yun Y, Li H, Hou L, Han M, Li G (2010) SO2 inhalation contributes to the development and progression of ischemic stroke in the brain. Toxicol Sci 114:226–236
Scarpulla RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576:1–14
Scarpulla RC (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97:673–683
Shapiro R (1977) Genetic effects of bisulfate (sulfur dioxide). Mutat Res 38:149–176
Shi X (1994) Generation of SO3 − and OH radical in SO3 2− reactions with inorganic environmental pollutants and its implications to SO3 2− toxicity. J Inorg Biochem 56:155–165
Shi M, Mao Y (1994) 8-Hydroxy-2′-deoxyguanosine formation and DNA damage induced by sulfur trioxide anion radicals. Biochem Biophys Res Commun 205:141–147
Sohn EJ, Kim J, Hwang Y, Im S, Moon Y, Kang DM (2012) TGF-β suppresses the expression of genes related to mitochondrial function in lung A549 cells. Cell Mol Biol (Noisy-le-grand) 58:OL1763–OL1767
Valerio A, Cardile A, Cozzi V, Bracale R, Tedesco L, Pisconti A, Palomba L, Cantoni O, Clementi E, Moncada S, Carruba MO, Nisoli E (2006) TNF-α downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents. J Clin Invest 116:2791–2798
Velayutham M, Hemann CF, Cardounel AJ, Zweier JL (2016) Sulfite oxidase activity of cytochrome c: role of hydrogen peroxide. Biochem Biophys Rep 5:96–104
Wang CH, Wu SB, Wu YT, Wei YH (2013) Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Exp Biol Med (Maywood) 238:450–460
Weber KC, Visscher MB (1969) Metabolism of the isolated canine lung. Amer J Physiol 217:1044–1052
Yeh DY, Fu YH, Yang YC, Wang JJ (2014) Resveratrol alleviates lung ischemia and reperfusion-induced pulmonary capillary injury through modulating pulmonary mitochondrial metabolism. Transplant Proc 46:1131–1134
Yun Y, Hou L, Sang N (2011) SO(2) inhalation modulates the expression of pro-inflammatory and pro-apoptotic genes in rat heart and lung. J Hazard Mater 185:482–488
Zhang L, Bao Y, Li J (2011) Nuclear respiratory factor-1 is involved in mitochondrial dysfunction induced by benzo(a)pyrene in human bronchial epithelial cells. Basic Clin Pharmacol Toxicol 109:115–122
Acknowledgments
This research was supported by the National Natural Science Foundation of China (21007036, 91543203, 21222701, 21377076), Guangzhou Key Laboratory of Environmental Exposure and Health (no. GZKLEEH201612), Research Project Supported by Shanxi Scholarship Council of China [grant number 2015-006], Program for the Top Young Academic Leaders of Higher Learning Institutions of Shanxi [grant number 20120303], and Nature Science Foundation of Shanxi Province [grant number 2012011036-6].
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Qin, G., Wang, J. & Sang, N. Sulfur dioxide inhibits expression of mitochondrial oxidative phosphorylation genes encoded by both nuclear DNA and mitochondrial DNA in rat lungs. Environ Sci Pollut Res 24, 2527–2534 (2017). https://doi.org/10.1007/s11356-016-7859-7
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DOI: https://doi.org/10.1007/s11356-016-7859-7


